tbuckley/cabot-search huggingface dataset:
Wnt signaling in liver regeneration, disease, and cancer
Authors: Gengyi Zou, Jae-Il Park
Journal: Clinical and Molecular Hepatology (2022)

The liver exhibits the highest recovery rate from acute injuries. However, in chronic liver disease, the long-term loss of hepatocytes often leads to adverse consequences such as fibrosis, cirrhosis, and liver cancer. The Wnt signaling plays a pivotal role in both liver regeneration and tumorigenesis. Therefore, manipulating the Wnt signaling has become an attractive approach to treating liver disease, including cancer. Nonetheless, given the crucial roles of Wnt signaling in physiological processes, blocking Wnt signaling can also cause several adverse effects. Recent studies have identified cancer-specific regulators of Wnt signaling, which would overcome the limitation of Wnt signaling target approaches. In this review, we discussed the role of Wnt signaling in liver regeneration, precancerous lesion, and liver cancer. Furthermore, we summarized the basic and clinical approaches of Wnt signaling blockade and proposed the therapeutic prospects of cancer-specific Wnt signaling blockade for liver cancer treatment.
Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements
Authors: Damir Baranasic, Matthias Hörtenhuber, Piotr J. Balwierz, Tobias Zehnder, Abdul Kadir Mukarram, Chirag Nepal, Csilla Várnai, Yavor Hadzhiev, Ada Jimenez-Gonzalez, Nan Li, Joseph Wragg, Fabio M. D’Orazio, Dorde Relic, Mikhail Pachkov, Noelia Díaz, Benjamín Hernández-Rodríguez, Zelin Chen, Marcus Stoiber, Michaël Dong, Irene Stevens, Samuel E. Ross, Anne Eagle, Ryan Martin, Oluwapelumi Obasaju, Sepand Rastegar, Alison C. McGarvey, Wolfgang Kopp, Emily Chambers, Dennis Wang, Hyejeong R. Kim, Rafael D. Acemel, Silvia Naranjo, Maciej Łapiński, Vanessa Chong, Sinnakaruppan Mathavan, Bernard Peers, Tatjana Sauka-Spengler, Martin Vingron, Piero Carninci, Uwe Ohler, Scott Allen Lacadie, Shawn M. Burgess, Cecilia Winata, Freek van Eeden, Juan M. Vaquerizas, José Luis Gómez-Skarmeta, Daria Onichtchouk, Ben James Brown, Ozren Bogdanovic, Erik van Nimwegen, Monte Westerfield, Fiona C. Wardle, Carsten O. Daub, Boris Lenhard, Ferenc Müller
Journal: Nature Genetics (2022)

Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center ( https://danio-code.zfin.org ) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals.
The impact of COVID-19 vaccination programme in the Republic of San Marino: Focus on effectiveness of Gam-Covid-Vac
Authors: Giuseppe Tonnara, Pierluca Piselli, Claudia Cimaglia, Massimo Arlotti, Elena Sacchini, Samanta Manoni, Antonio Zani, Fausto Muccioli, Anna Laderchi, Sergio Rabini, Andrea Antinori, Francesco Vaia, Emanuele Nicastri, Enrico Girardi
Journal: Clinical Microbiology and Infection (2022)
Cold versus hot EMR for large duodenal adenomas
Authors: Alessandro Repici, Antonio Capogreco, Spadaccini Marco, Roberta Maselli, Piera Alessia Galtieri, Alessandro Fugazza, Silvia Carrara, matteo colombo, Guido Schachschal, Anna Creutzfeldt, Shahila Perveen Aslam, Asma Alkandari, Pradeep Bhandari, Alexander Meining, Cesare Hassan, Thomas Rösch
Journal: Gut (2022)
Single-cell analysis of the aging female mouse hypothalamus
Authors: Kaitlyn H. Hajdarovic, Doudou Yu, Lexi-Amber Hassell, Shane A. Evans, Sarah Packer, Nicola Neretti, Ashley E. Webb
Journal: Nature Aging (2022)

Alterations in metabolism, sleep patterns, body composition, and hormone status are all key features of aging. While the hypothalamus is a well-conserved brain region that controls these homeostatic and survival-related behaviors, little is known about the intrinsic features of hypothalamic aging. Here, we perform single nuclei RNA-sequencing of 40,064 hypothalamic nuclei from young and aged female mice. We identify cell type-specific signatures of aging in neuronal subtypes as well as astrocytes and microglia. We uncover changes in cell types critical for metabolic regulation and body composition, and in an area of the hypothalamus linked to cognition. Our analysis also reveals an unexpected female-specific feature of hypothalamic aging: the master regulator of X-inactivation, Xist, is elevated with age, particularly in hypothalamic neurons. Moreover, using machine learning, we show that levels of X-chromosome genes, and Xist itself, can accurately predict cellular age. This study identifies critical cell-specific changes of the aging hypothalamus in mammals, and uncovers a potential marker of neuronal aging in females.
Reply
Authors: Coralie Amadou, Oumarou Nabi, Lawrence Serfaty, Karine Lacombe, Jérôme Boursier, Philippe Mathurin, Céline Ribet, Victor de Ledinghen, Marie Zins, Marie‐Aline Charles
Journal: Hepatology (2022)

We appreciate the opportunity to respond to Mondia et al. This comment raises concerns about preterm birth analysis, which comprised a subgroup of our study population. First, Mondia et al. point out the lack of information on hospital admission and duration in the neonatal period. The Constances cohort included adult participants ≥18 years old. Birth data were retrospectively collected from health booklets. Indeed, information about neonatal hospitalization information is not always detailed in health booklets and therefore was not collected for the cohort. Second, regarding breastfeeding and early weight catch‐up, there were missing data in our sample. We are currently performing a data cleaning for these variables, but we expect availability for only a subset of the cohort. We agree with Mondia et al. that this data analysis would improve the comprehension of the impact of preterm birth and low birth weight on future health. Finally, congenital or genetic disorders (not accounted for in this analysis) represent a minor cause of prematurity/low birth weight. Nevertheless, we would like to correct the comment regarding metabolic disorders given that we did account for metabolic syndrome in participants through a mediation analysis. Finally, liver biopsy was not considered in this general purposed and observational cohort. However, common causes of liver fibrosis (other than NAFLD) were systematically searched for through a physician‐administrated questionnaire. People with chronic viral hepatitis or excessive alcohol consumption (i.e., >20 and >30 g per day for women and men, respectively) were excluded from our analyses.
People who develop alopecia areata have an increased risk for depression, anxiety, time off work and unemployment
Journal: British Journal of Dermatology (2022)

Alopecia areata is a form of hair loss that most often occurs in patches on the scalp. It affects about 1 in 4000 people every year, and some people have total hair loss on their scalp and body. Because hair loss is so visible, it can have an impact on day‐to‐day life and may lead to mental health problems. We wanted to find out if people with alopecia areata were more likely to have anxiety and depression, or if they are more likely to have time off work or be unemployed.
Safety Implications of Switching Pembrolizumab Dosage From 200 mg Every 3 Weeks to 400 mg Every 6 Weeks in Patients With Advanced NSCLC
Authors: Ryoko Inaba Higashiyama, Tatsuya Yoshida, Shigehiro Yagishita, Mayu Ohuchi, Naomi Sakiyama, Masahiro Torasawa, Masayuki Shirasawa, Ken Masuda, Yuki Shinno, Yuji Matsumoto, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Akinobu Hamada, Yuichiro Ohe
Journal: Journal of Thoracic Oncology (2022)
Frail older people and those in deprived areas remain at risk from covid-19, even after vaccination
Authors: Helen Saul, Deniz Gursul, Michela Antonelli, Claire Steves
Journal: BMJ (2022)

The studyAntonelli M, Penfold RS, Merino J, et al. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet Infect Dis 2022;22:1.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/older-people-at-risk-from-covid-even-after-vaccine/.
Time Outdoors in Reducing Myopia
Authors: Xiangui He, Padmaja Sankaridurg, Jingjing Wang, Jun Chen, Thomas Naduvilath, Mingguang He, Zhuoting Zhu, Wayne Li, Ian G. Morgan, Shuyu Xiong, Jianfeng Zhu, Haidong Zou, Kathryn A. Rose, Bo Zhang, Rebecca Weng, Serge Resnikoff, Xun Xu
Journal: Ophthalmology (2022)

To evaluate the efficacy of time outdoors per school day over 2 years on myopia onset and shift.A prospective, cluster-randomized, examiner-masked, 3-arm trial.A total of 6295 students aged 6 to 9 years from 24 primary schools in Shanghai, China, stratified and randomized by school in a 1:1:1 ratio to control (n = 2037), test I (n = 2329), or test II (n = 1929) group.An additional 40 or 80 minutes of outdoor time was allocated to each school day for test I and II groups. Children in the control group continued their habitual outdoor time. Objective monitoring of outdoor and indoor time and light intensity each day was measured with a wrist-worn wearable during the second-year follow-up.The 2-year cumulative incidence of myopia (defined as cycloplegic spherical equivalent [SE] of ≤-0.5 diopters [D] in the right eye) among the students without myopia at baseline and changes in SE and axial length (AL) after 2 years.The unadjusted 2-year cumulative incidence of myopia was 24.9%, 20.6%, and 23.8% for control, test I, and II groups, respectively. The adjusted incidence decreased by 16% (incidence risk ratio [IRR], 0.84; 95% confidence interval [CI], 0.72-0.99; P = 0.035) in test I and 11% (IRR = 0.89; 95% CI, 0.79-0.99; P = 0.041) in test II when compared with the control group. The test groups showed less myopic shift and axial elongation compared with the control group (test I: -0.84 D and 0.55 mm, test II: -0.91 D and 0.57 mm, control: -1.04 D and 0.65 mm). There was no significant difference in the adjusted incidence of myopia and myopic shift between the 2 test groups. The test groups had similar outdoor time and light intensity (test I: 127 ± 30 minutes/day and 3557 ± 970 lux/minute; test II: 127 ± 26 minutes/day and 3662 ± 803 lux/minute) but significantly more outdoor time and higher light intensity compared with the control group (106 ± 27 minutes/day and 2984 ± 806 lux/minute). Daily outdoor time of 120 to 150 minutes at 5000 lux/minutes or cumulative outdoor light intensity of 600 000 to 750 000 lux significantly reduced the IRR by 15%～ 24%.Increasing outdoor time reduced the risk of myopia onset and myopic shifts, especially in nonmyopic children. The protective effect of outdoor time was related to the duration of exposure and light intensity. The dose-response effect between test I and test II was not observed probably because of insufficient outdoor time achieved in the test groups, which suggests that proper monitoring on the compliance on outdoor intervention is critical if one wants to see the protective effect.
Genetic variation in<i>TERT</i>modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study
Authors: Stephan Buch, Hamish Innes, Philipp Ludwig Lutz, Hans Dieter Nischalke, Jens U Marquardt, Janett Fischer, Karl Heinz Weiss, Jonas Rosendahl, Astrid Marot, Marcin Krawczyk, Markus Casper, Frank Lammert, Florian Eyer, Arndt Vogel, Silke Marhenke, Johann von Felden, Rohini Sharma, Stephen Rahul Atkinson, Andrew McQuillin, Jacob Nattermann, Clemens Schafmayer, Andre Franke, Christian Strassburg, Marcella Rietschel, Heidi Altmann, Stefan Sulk, Veera Raghavan Thangapandi, Mario Brosch, Carolin Lackner, Rudolf E Stauber, Ali Canbay, Alexander Link, Thomas Reiberger, Mattias Mandorfer, Georg Semmler, Bernhard Scheiner, Christian Datz, Stefano Romeo, Stefano Ginanni Corradini, William Lucien Irving, Joanne R Morling, Indra Neil Guha, Eleanor Barnes, M Azim Ansari, Jocelyn Quistrebert, Luca Valenti, Sascha A Müller, Marsha Yvonne Morgan, Jean-François Dufour, Jonel Trebicka, Thomas Berg, Pierre Deltenre, Sebastian Mueller, Jochen Hampe, Felix Stickel
Journal: Gut (2022)

Objective Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Design Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case–control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Results Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10 −9 , OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10 −5 , OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10 −44 ). Conclusion This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
PD-1 signaling facilitates activation of lymphoid tissue inducer cells by restraining fatty acid oxidation
Authors: Di Wu, Luni Hu, Mengwei Han, Yichen Deng, Yime Zhang, Guanqun Ren, Xingyu Zhao, Zongxian Li, Peng Li, Yinlian Zhang, Shanwen Chen, Jun Li, Yanyan Shi, Jianxin Xue, Pengyuan Wang, Chao Zhong
Journal: Nature Metabolism (2022)
BLITZ‐HF: a nationwide initiative to evaluate and improve adherence to acute and chronic heart failure guidelines
Authors: Michele Massimo Gulizia, Francesco Orso, Andrea Mortara, Donata Lucci, Nadia Aspromonte, Leonardo De Luca, Giuseppe Di Tano, Giuseppe Leonardi, Alessandro Navazio, Giovanni Pulignano, Furio Colivicchi, Andrea Di Lenarda, Fabrizio Oliva
Journal: European Journal of Heart Failure (2022)

To assess adherence to guideline recommendations among a large network of Italian cardiology sites in the management of acute and chronic heart failure (HF) and to evaluate if an ad-hoc educational intervention can improve their performance on several pharmacological and non-pharmacological indicators.BLITZ-HF was a cross-sectional study based on a web-based recording system with pop-up reminders on guideline recommendations used during two 3-month enrolment periods carried out 3 months apart (Phase 1 and 3), interspersed by face-to-face macro-regional benchmark analyses and educational meetings (Phase 2). Overall, 7218 patients with acute and chronic HF were enrolled at 106 cardiology sites. During the enrolment phases, 3920 and 3298 patients were included, respectively, 84% with chronic HF and 16% with acute HF in Phase 1, and 74% with chronic HF and 26% with acute HF in Phase 3. At baseline, adherence to guideline recommendations was already overall high for most indicators. Among acute HF patients, an improvement was obtained in three out of eight indicators, with a significant rise in echocardiographic evaluation. Among chronic HF patients with HF and preserved or mid-range ejection fraction, performance increased in two out of three indicators: creatinine and echocardiographic evaluations. An overall performance improvement was observed in six out of nine indicators in ambulatory HF with reduced ejection fraction patients with a significant increase in angiotensin receptor-neprilysin inhibitor prescription rates.Within a context of an already elevated level of adherence to HF guideline recommendations, a structured multifaceted educational intervention could be useful to improve performance on specific indicators. Extending this approach to other non-cardiology healthcare professionals, who usually manage patients with HF, should be considered.
The impact of type 2 immunity and allergic diseases in atherosclerosis
Authors: Nieves Fernández‐Gallego, Raquel Castillo‐González, Nerea Méndez‐Barbero, Celia López‐Sanz, David Obeso, Alma Villaseñor, María M. Escribese, Beatriz López‐Melgar, Jorge Salamanca, Amparo Benedicto‐Buendía, Luis Jesús Jiménez‐Borreguero, Borja Ibañez, Joaquín Sastre, María Teresa Belver, Francisco Vega, Carlos Blanco, Domingo Barber, Francisco Sánchez‐Madrid, Hortensia de la Fuente, Pilar Martín, Vanesa Esteban, Rodrigo Jiménez‐Saiz
Journal: Allergy (2022)

Abstract Allergic diseases are allergen‐induced immunological disorders characterized by the development of type 2 immunity and IgE responses. The prevalence of allergic diseases has been on the rise alike cardiovascular disease (CVD), which affects arteries of different organs such as the heart, the kidney and the brain. The underlying cause of CVD is often atherosclerosis, a disease distinguished by endothelial dysfunction, fibrofatty material accumulation in the intima of the artery wall, smooth muscle cell proliferation, and Th1 inflammation. The opposed T‐cell identity of allergy and atherosclerosis implies an atheroprotective role for Th2 cells by counteracting Th1 responses. Yet, the clinical association between allergic disease and CVD argues against it. Within, we review different phases of allergic pathology, basic immunological mechanisms of atherosclerosis and the clinical association between allergic diseases (particularly asthma, atopic dermatitis, allergic rhinitis and food allergy) and CVD. Then, we discuss putative atherogenic mechanisms of type 2 immunity and allergic inflammation including acute allergic reactions (IgE, IgG1, mast cells, macrophages and allergic mediators such as vasoactive components, growth factors and those derived from the complement, contact and coagulation systems) and late phase inflammation (Th2 cells, eosinophils, type 2 innate‐like lymphoid cells, alarmins, IL‐4, IL‐5, IL‐9, IL‐13 and IL‐17).
Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences
Authors: Lei Pang, Xi Jiang, Xin Lian, Jie Chen, Er-Fei Song, Lei-Gang Jin, Zheng-Yuan Xia, Hai-Chun Ma, Yin Cai
Journal: Military Medical Research (2022)

Abstract The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease (CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction (CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas: (1) mechanisms underlying age-related cardiac remodeling; (2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women; (3) we select a few polyphenol or polyamine rich compounds as the CR-mimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.
Reply to “Response to Pathoulas et al’s ‘Evaluation of standardized scalp photography on patient perception of hair loss severity, anxiety, and treatment’”
Authors: James T. Pathoulas, Kelly E. Flanagan, Chloe J. Walker, Isabel Pupo Wiss, Ehsan Azimi, Maryanne M. Senna
Journal: Journal of the American Academy of Dermatology (2022)
Corrigendum to “Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis” [Biomater. 161 (2018) 164–178]
Authors: Xin Cui, Renee-Tyler Tan Morales, Weiyi Qian, Haoyu Wang, Jean-Pierre Gagner, Igor Dolgalev, Dimitris Placantonakis, David Zagzag, Luisa Cimmino, Matija Snuderl, Raymond H W Lam, Weiqiang Chen
Journal: Biomaterials (2022)
Minimally Clinically Important Difference in Health Status Scores in Patients With HFrEF vs HFpEF
Authors: Javed Butler, Muhammad Shahzeb Khan, JoAnn Lindenfeld, William T Abraham, Gianluigi Savarese, Afshin Salsali, Cordula Zeller, Barbara Peil, Gerasimos Filippatos, Piotr Ponikowski, Stefan D Anker
Journal: JACC Heart Failure (2022)

Differences in clinically important thresholds in patient-reported outcomes measures such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) remain less well-established in patients with heart failure with preserved ejection fraction (HFpEF) versus heart failure with reduced ejection fraction (HFrEF).The purpose of this study was to estimate meaningful thresholds for improvement or deterioration in the KCCQ-Total Symptom Score (TSS) in patients with HFrEF versus HFpEF.This secondary analysis of EMPERIAL program used anchor- and distribution-based approaches to estimate thresholds for improvement or deterioration in the KCCQ-TSS using Patient Global Impression of Severity (PGIS) as the primary anchor. Mean change in KCCQ-TSS from baseline to week 12 was calculated for each PGIS.A total of 312 HFrEF and 315 HFpEF patients were enrolled. At week 12, mean changes in KCCQ-TSS corresponding to PGIS changes of "any improvement," "1-category improvement," and "1-category deterioration" were 13 ± 17, 12 ± 17, -3 ± 16 points in HFrEF, and 15 ± 18, 13 ± 17, -7 ± 18 points in HFpEF. Threshold for meaningful within-patient change in KCCQ-TSS was ≥9 points in HFrEF and ≥7 points in HFpEF patients. Sensitivity and specificity of ≥9 points/≥7 points change was 0.65 and 0.70 for HFrEF and 0.64 and 0.66 for HFpEF. Cumulative distribution function curves of KCCQ-TSS change from baseline to week 12 showed a shift to higher scores in both HFrEF and HFpEF patients.In the EMPERIAL program, a change in KCCQ-TSS of ≥9 points in HFrEF and ≥7 points in HFpEF represents the minimal clinically important difference for improvement, confirming the broad range of 5-10 points as meaningful thresholds.